Bone marrow is a dose-limiting normal tissue for both chemotherapy and wide-field irradiation. These laboratory investigations study the response of hematopoietic stem cells to these agents. We have devised a simple technique to measure the self-renewal capacity of the stem cell compartment. Data, thus far, indicate that this self-renewal capacity is limited and not indefinite. Further, following cytotoxic agents, there appears to be a permanent reduction in this. From the studies reported, a new model of the stem cell compartment has been derived. During the course of these studies, we have had the opportunity to observe the late effects of cytotoxic agents on a population of mice. These have resulted in a number of other important findings including hair-graying, cataracts, tumor induction and life shortening.